title: Glutamine induces heat-shock protein-70 and glutathione expression and attenuates ischemic damage in rat islets.
abstract: BACKGROUND
  The transplantation of isolated islets is believed to be an attractive approach for cure of diabetes mellitus. Heat-shock protein (HSP70), which plays a vital role in cellular protection, has been detected in various tissues subjected to stress. Glutamine (GLN) is an important cellular fuel and an essential precursor for the antioxidant glutathione (GSH). It is believed to enhance cellular survival against a variety of stressful stimuli through HSP70. Thus, we performed this study to examine the hypothesis that preoperative GLN administration induces HSP70 and GSH expression before islet transplantation attenuating ischemic damage to rat islets.
  
  
  METHODS
  Adult male Sprague-Dawley (SD) rats were randomly divided into two groups according to the administration of GLN after islet isolation. Group A served as the controls, receiving no GLN. Group B islet cells were cultured with L-GLN (10 mmol/L) supplementation for 24 hours. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed in islet cells by Western blots. Isolated rat islets were cultured with interleukin (IL)-1beta. Nitrite production was measured using the Griess reagent.
  
  
  RESULTS
  The GSH levels were significantly elevated in the glutamine-treated group. HSP70 expression in islets treated with GLN was markedly stronger compared with the control group. The basal Bcl-2 expression was markedly increased by GLN treatment. The GLN-treated group showed attenuated IL-1beta-induced injury in association with NO production.
  
  
  CONCLUSIONS
  These results suggested that preoperative GLN administration induced HSP70 and GSH expressions before islet transplantation, thus attenuating IL-1beta-induced injury in association with NO production and apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early inflammation at the site of implantation through a self-protective mechanism.
authors.affiliation: Department of Surgery, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea. jhj@gnah.co.kr
authors.forename: H J
authors.initials: HJ
authors.lastname: Jang
authors.forename: J H
authors.initials: JH
authors.lastname: Kwak
authors.forename: E Y
authors.initials: EY
authors.lastname: Cho
authors.forename: Y M
authors.initials: YM
authors.lastname: We
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: S C
authors.initials: SC
authors.lastname: Kim
authors.forename: D J
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007511:Ischemia / Q000517:prevention & control*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018840:HSP70 Heat-Shock Proteins; D007328:Insulin; D005973:Glutamine; D005978:Glutathione; D005947:Glucose